The Baltimore Longitudinal Study on Aging (BLSA) is conducted by investigators in the NIA Intramural Research Program. The BLSA is America's longest-running scientific study of human aging. More than 1,250 men and women, ranging in age from the twenties to the nineties, are active participants in this study from more of 3000 that were enrolled. Since its inception in 1958, the BLSA has generated numerous findings not only on the normal course of aging, but also disentangling the effects of disease from the normal aging process. More recently, the BLSA is collecting data that explore the multifactorial pathways that lead to decline of physical and cognitive function with aging. In 2002-2003 NIA investigators produced a new framework for the BLSAs scientific agenda. While the study will retain many of its research goals and objectives, the investigators plan to place a strong emphasis on future recruitment of successful agers, or those who at age 75 have few, if any, age-associated diseases or disabilities. This will permit the study to more intensely investigate factors that predict healthy aging and health-related outcomes across the life-span, to identify strategies for successful adaptation to aging, and to develop hypotheses concerning possible targets for intervention that may positively affect specific aging phenotypes and prevent age-related diseases. In addition, BLSA investigators are working to facilitate cross-sectional and longitudinal analyses that will increase our understanding of how changes in various parameters affect aging, age-related disease, and the development of frailty and disability. NIA investigators also conduct small, focused and in depth clinical studies aimed at testing some of the hypotheses developed in the context of the BLSA, and facilitate their clinical translation using the Translational Research Section.